Phase 1 open-label, dose-escalation and dose-expansion study of INI-4001 as a single agent and in combination with approved checkpoint inhibitors in subjects with advanced solid tumors.

Start Date29 Mar 2024

Sponsor / Collaborator

Inimmune Corp.Startup

[+1]

100 Clinical Results associated with INI-4001

100 Translational Medicine associated with INI-4001

100 Patents (Medical) associated with INI-4001

Literatures (Medical) associated with INI-4001

npj Vaccines

A lipidated TLR7/8 adjuvant enhances the efficacy of a vaccine against fentanyl in mice

Article

Author: Crouse, Bethany ; Pravetoni, Marco ; Miller, Shannon M ; Burkhart, David J ; Bazin, Helene G ; Amin, Hardik ; Hicks, Linda ; Evans, Jay T ; Cole, Shelby

AbstractOpioid use disorders (OUD) and opioid-related fatal overdoses are a public health concern in the United States. Approximately 100,000 fatal opioid-related overdoses occurred annually from mid-2020 to the present, the majority of which involved fentanyl or fentanyl analogs. Vaccines have been proposed as a therapeutic and prophylactic strategy to offer selective and long-lasting protection against accidental or deliberate exposure to fentanyl and closely related analogs. To support the development of a clinically viable anti-opioid vaccine suitable for human use, the incorporation of adjuvants will be required to elicit high titers of high-affinity circulating antibodies specific to the target opioid. Here we demonstrate that the addition of a synthetic TLR7/8 agonist, INI-4001, but not a synthetic TLR4 agonist, INI-2002, to a candidate conjugate vaccine consisting of a fentanyl-based hapten, F1, conjugated to the diphtheria cross-reactive material (CRM), significantly increased generation of high-affinity F1-specific antibody concentrations, and reduced drug distribution to the brain after fentanyl administration in mice.

Pharmaceutics

Using Dual Toll-like Receptor Agonism to Drive Th1-Biased Response in a Squalene- and α-Tocopherol-Containing Emulsion for a More Effective SARS-CoV-2 Vaccine

Article

Author: Short, Kristopher K. ; Tee, Rebekah D. ; Burkhart, David J. ; Kaiser, Johnathan A. ; Lorentz, Elizabeth B. ; Evans, Jay T. ; Lathrop, Stephanie K. ; Davison, Clara J. ; Partlow, Haley A.

A diversity of vaccines is necessary to reduce the mortality and morbidity of SARS-CoV-2. Vaccines must be efficacious, easy to manufacture, and stable within the existing cold chain to improve their availability around the world. Recombinant protein subunit vaccines adjuvanted with squalene-based emulsions such as AS03™ and MF59™ have a long and robust history of safe, efficacious use with straightforward production and distribution. Here, subunit vaccines were made with squalene-based emulsions containing novel, synthetic toll-like receptor (TLR) agonists, INI-2002 (TLR4 agonist) and INI-4001 (TLR7/8 agonist), using the recombinant receptor-binding domain (RBD) of SARS-CoV-2 S protein as an antigen. The addition of the TLR4 and TLR7/8 agonists, alone or in combination, maintained the formulation characteristics of squalene-based emulsions, including a sterile filterable droplet size (<220 nm), high homogeneity, and colloidal stability after months of storage at 4, 25, and 40 °C. Furthermore, the addition of the TLR agonists skewed the immune response from Th2 towards Th1 in immunized C57BL/6 mice, resulting in an increased production of IgG2c antibodies and a lower antigen-specific production of IL-5 with a higher production of IFNγ by lymphocytes. As such, incorporating TLR4 and TLR7/8 agonists into emulsions leveraged the desirable formulation and stability characteristics of emulsions and can induce Th1-type humoral and cell-mediated immune responses to combat the continued threat of SARS-CoV-2.

Vaccines

Co-Delivery of Novel Synthetic TLR4 and TLR7/8 Ligands Adsorbed to Aluminum Salts Promotes Th1-Mediated Immunity against Poorly Immunogenic SARS-CoV-2 RBD

Article

Author: Siram, Karthik ; Davison, Clara J. ; Tee, Rebekah ; Partlow, Haley A. ; Abdelwahab, Walid M. ; Lathrop, Stephanie K. ; Burkhart, David J. ; Evans, Jay T.

Despite the availability of effective vaccines against COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide, pressing the need for new vaccines with improved breadth and durability. We developed an adjuvanted subunit vaccine against SARS-CoV-2 using the recombinant receptor–binding domain (RBD) of spikes with synthetic adjuvants targeting TLR7/8 (INI-4001) and TLR4 (INI-2002), co-delivered with aluminum hydroxide (AH) or aluminum phosphate (AP). The formulations were characterized for the quantities of RBD, INI-4001, and INI-2002 adsorbed onto the respective aluminum salts. Results indicated that at pH 6, the uncharged RBD (5.73 ± 4.2 mV) did not efficiently adsorb to the positively charged AH (22.68 ± 7.01 mV), whereas it adsorbed efficiently to the negatively charged AP (−31.87 ± 0.33 mV). Alternatively, pre-adsorption of the TLR ligands to AH converted it to a negatively charged particle, allowing for the efficient adsorption of RBD. RBD could also be directly adsorbed to AH at a pH of 8.1, which changed the charge of the RBD to negative. INI-4001 and INI-2002 efficiently to AH. Following vaccination in C57BL/6 mice, both aluminum salts promoted Th2-mediated immunity when used as the sole adjuvant. Co-delivery with TLR4 and/or TLR7/8 ligands efficiently promoted a switch to Th1-mediated immunity instead. Measurements of viral neutralization by serum antibodies demonstrated that the addition of TLR ligands to alum also greatly improved the neutralizing antibody response. These results indicate that the addition of a TLR7/8 and/or TLR4 agonist to a subunit vaccine containing RBD antigen and alum is a promising strategy for driving a Th1 response and neutralizing antibody titers targeting SARS-CoV-2.

News (Medical) associated with INI-4001

24 Jul 2024

·www.prnewswire.com

INIMMUNE ANNOUNCES FIRST CANCER PATIENT DOSED IN PHASE 1 CLINICAL STUDY USING THE IMMUNOTHERAPEUTIC INI-4001, A NOVEL TLR7/8 AGONIST

MISSOULA, Mont., July 24, 2024 /PRNewswire/ -- Inimmune, a clinical stage biotech company focused on the development of novel immunotherapies, vaccines, and vaccine adjuvants announced today the dosing of the first patient in its Phase 1 single ascending dose study of INI-4001 in patients with advanced solid tumors. This is an open-label, multiple-ascending dose, two-part dose ranging and cohort expansion study of INI-4001 in patients with advanced solid tumors. This first-in-human trial of INI-4001, Inimmune's proprietary TLR7/8 agonist in a nanoparticle delivery system, will consist of two parts. In Phase 1a, single dose escalation cohorts receiving monotherapy INI-4001 will determine PK, safety, and tolerability. This is followed by Phase 1b where patients who have progressed or have stable disease after 3 cycles of INI-4001 will be allowed to receive concurrent administration of an anti-PD-1 or anti-PD-L1 immunotherapy plus INI-4001. In pre-clinical studies, INI-4001 was efficacious both as a monotherapy and in combination with anti-PD-1 checkpoint therapy in syngeneic murine tumors (LLC, MC38 and B16F10). Additionally, INI-4001 has been shown to induce production of the cytokine IFNα and activation of antigen presenting cells, leading to downstream T cell activation in vivo. INI-4001 may prove to be an ideal combination agent with checkpoint inhibitors given that a minority of patients currently benefit from checkpoint inhibitor monotherapy. Inimmune's CEO, Alan Joslyn, said "We are very excited that INI-4001 clinical trials have commenced, as this marks an important milestone for our company and oncology patients. INI-4001 either as monotherapy or in combination with checkpoint therapy can potentially provide physicians a new therapeutic option in their treatment toolbox." Inimmune's trial of INI-4001 is being conducted in Australia and is expected to be complete by the end of 2025. Additional information can be found at clinicaltrials.gov (NCT06302426). About Inimmune: Inimmune Corp. (Missoula, MT) is a privately held clinical stage biotechnology company focused on the discovery and development of novel immunotherapies, vaccines, and vaccine adjuvants. Inimmune is harnessing the human immune system to create safe and effective treatments for allergy, infectious disease, autoimmunity and cancer. Their laboratories and offices are housed in the Montana Technology Enterprise Center (MonTEC) in Missoula. For more information on Inimmune's research and development of novel vaccine adjuvants and delivery systems, please visit . Contact: Media Relations Inimmune Corporation Phone: (406)-541-5913 Email: [email protected] SOURCE Inimmune Corporation

ImmunotherapyPhase 1Vaccine

100 Deals associated with INI-4001

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Phase 1	AU	Inimmune Corp.Startup	29 Mar 2024
Neoplasms	IND Application	US	Inimmune Corp.Startup	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

INI-4001

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation